1. Field of the Invention
The present invention relates to probe arrays for use in detecting peptides, proteins and DNAs, diagnosing, and analyzing biological materials including DNAs; and methods and apparatuses to produce the same.
2. Description of the Related Art
For DNA analyses or DNA tests or diagnoses, amplification of a small amount of DNA, isolation and identification of the amplified DNA fragments, and other procedures are necessary. For DNA amplification, PCR (polymerase chain reaction) is widely used, in which an extremely small number of DNAs can be multiplied by several orders of magnitude so as to be detectable. On the other hand, for the isolation and detection of different DNAs, among other methods, a DNA sequencer and fragment analyzer, in which gel electrophoresis and fluorescence detection are combined, are used. However, electrophoresis becomes very labor-intensive as the number of samples or test items increases. Thus, a simple method using DNA probes is drawing attention, in particular, a DNA chip, in which many kinds of probes are immobilized on the surface of a solid to make a probe array which undergoes hybridization with the sample, then only specific DNAs are trapped on the surface of the solid and detected (Nature Medicine 2, 753, 1996).
The probe detection method is used also for the analysis of proteins or peptides or various biological materials which interact with them, and a peptide chip corresponding to the DNA chip is now being used. This kind of isolation and detection method, in which a peptide or DNA is immobilized on the surface of a solid and hybridization proceeds between the peptide or DNA and a sample, has long been known as a blotting method in which the presence of the target DNA or the like is detected by a probe immobilized on a membrane using radioactive labeling. However, the DNA chip, on which a large number of probes can be immobilized on a small area (1 cm2) of the surface of a solid such as glass or silicone, has the advantage in that only a small amount of sample is required, and a vast variety of probes can be used simultaneously. Methods for the production of DNA chips are divided broadly into two groups. In the first group, a DNA probe is synthesized one base at a time by a photochemical reaction on small segments (0.05 mm2 to 0.2 mm2) of a solid using the same photomasking technique as used for semiconductors or the like (Science 251, 767, 1991). In the second group, a synthesized DNA, PCR-amplified DNA, or DNA obtained by cloning is immobilized on a small segment of the surface of a solid for each segment of individual probes (Nature Biotech 16, 27, 1998). The latter has the advantage that a peptide chip or DNA chip with the required probes can be made relatively easily, and is the method of choice of many startup companies.